The present invention relates to an apparatus and method for providing x-ray therapy in humans. More specifically, the present invention relates to an apparatus and method for providing in-situ radiation treatment that utilizes a miniature energy transducer to produce x-rays, wherein the energy transducer defines a cavity that communicates with an evacuation opening and is continuously evacuated through a flexible tube by a dynamic pumping mechanism in order to maintain a desired vacuum level.
Restenosis is a heart condition that afflicts 35%-50% of all people who undergo balloon angioplasty to improve blood flow in narrowed sclerotic arteries. The condition consists of a significant re-closing of the treated artery segment hours to several months after the procedure. As a result, the arterial lumen size is decreased and the blood flow downstream from the lesion site is impaired. Consequently, patients afflicted with restenosis must undergo an additional balloon angioplasty, and in some cases a coronary bypass surgery must be performed. Aside from the pain and suffering of these patients, recurrent stenosis is also a serious economic burden on society, with estimated expenses as high as 3.0 billion dollars per year in the United States economy alone.
Attempts to treat restenosis have been concentrated in both the pharmacological and medical device areas. While pharmacological solutions have been proven effective in treating only acute restenosis, a condition developing immediately after balloon angioplasty, some progress has been made with medical devices in the treatment of long term restenosis, a condition that develops up to a few months following balloon angioplasty. An example for such medical device is the stent. Stents can be inserted into an occluded artery to hold it open. Stents have been shown to prevent two of the three mechanisms that cause recurrent stenosis, namely, elastic recoil of the artery and negative remodeling of the arterial structure. The third mechanism, neointimal growth, consists of hyper-proliferation of smooth muscle cells from the lesion into the lumen and is not prevented by stents.
Ionizing radiation holds great promise for treating restenosis. Ionizing radiation serves to damage undesirable hyper-proliferating tissue and ultimately to prevent the hyper-proliferation of smooth muscle cells in the irradiated region. Research has shown that gamma and beta radiation delivered at the location of stenotic lesions effectively stop both animal and human intimal proliferation. The effective, yet non-hazardous, required dose to treat human restenosis is between seven and forty Gray (mjoule/gram), preferably a dosage greater than fifteen Gray measured two mm from the center of the radiation source that penetrates the artery wall at a two mm depth over the lesion length.
In view of the above, various methods have been proposed to provide ionizing radiation treatment. For example, radiation catheters, based on the use of radioactive sources such as beta-emitting 32P, 90Sr/90Y, 188W/188Re, beta+emitting 48V or gamma emitting 192Ir, are at various stages of development and clinical evaluation. The radioactive sources, in a variety of configurations, are introduced to the treatment sites using special radiation catheters and the radioactive source is placed at the treatment site for a predetermined time period as to deliver the proper radiation dose. Radioactive stents are also used as alternative delivery means, incorporating some of the above radioactive isotopes.
The gamma and beta radioactive sources used by the present radiation catheters and radioactive stents, however, have several drawbacks including a limited ability to provide selective control over the dose distribution or overall radiation intensity, and the logistical, regulatory, and procedural difficulties involved in dealing with radioactive materials. In addition, gamma-emitting devices jeopardize patients by exposing healthy organs to dangerous radiation during the introduction of the radiation source. Hospital personnel that handle radioactive materials are also at risk due to exposure. In addition to the risks these devices impose on patients, hospital staff, and the environment, use of these devices invokes a regulatory burden due to the need to comply with nuclear regulatory requirements.
An additional approach to providing ionizing radiation treatment is through the use of an x-ray emitting energy transducer that is not radioactive. Conventional x-ray radiation for radiotherapy is produced by high-energy electrons generated and accelerated in a vacuum to impact a metal target. The emitted x-ray power is directly proportional to the electron beam current. However, the efficiency of x-ray generation is independent of electron current, but rather depends on the atomic number of the target material and on the acceleration voltage. Yet, another method for the production of x-rays is by direct conversion of light into x-ray radiation. It is known that the interaction of light with a target can produce highly energetic x-rays when the power densities achieved are in the range of 1016-1017 watt/cm . With the development of femtosecond laser, such power densities are achievable with moderate size lasers (See C. Tillman et al, NIMS in Phys. Res. A394 (1997), 387-396 and U.S. Pat. No. 5,606,588 issued to Umstadter et al., the contents of each of which are incorporated herein by reference). A 100 femtosecond, one mJ laser pulse focused down to a 3 micron spot, for example, will reach this power density level.
A variety of medical applications of the direct laser light conversion method of xray generation are currently in the development stage. The direct laser light conversion method, for example, has been considered for medical imaging (See, Herrlin K et al. Radiology (USA), vol. 189, no. 1, pp. 65-8, October 1993). Another medical application of femtosecond lasers is in improved non-thermal ablation of neural or eye tissue for surgical purposes (See, F. H. Loesel et al. Appl.Phys.B 66,121-128 (1998)). The development of compact table top models of femtosecond lasers makes laser generated x-rays an attractive alternative for radioactive material based radiotherapy.
Based on the above, an x-ray radiation treatment apparatus and method has been developed. In x-ray treatment an internal x-ray emitting miniature energy transducer generates x-rays in-situ. Co-pending and commonly assigned U.S. patent application Ser. No. 09/325,703 filed Jun. 3, 1999, and U.S. patent application Ser. No. 09/434,958 filed Nov. 5, 1999, describe miniaturized energy transducers that are coupled to flexible insertion devices to permit x-ray radiation treatment within the human body. Use of the miniaturized x-ray emitting energy transducer offers certain advantages with respect to intra vascular gamma and beta sources. These advantages are, but are not limited to, localization of radiation to the treatment site so that the treatment site may be irradiated with minimal damage to surrounding healthy tissue; reduction of hospital personnel risk due to exposure to radioactive materials; and minimization of the regulatory burden and additional costs that arise from the need to comply with nuclear regulatory requirements.
A variety of different types of cathode and anode structures have been proposed for the energy transducer. One proposal is to utilize a hollow cathode, which includes a cathode shell that defines a cavity. A light pulse is introduced into the cavity in order to heat an outer surface of the cathode shell, thereby causing thermionic emission of electrons from the outer surface. Another proposal for a hollow cathode incorporates the use of an electron escape nozzle, wherein an ion and electron plasma is generated in the cavity either by applying a light signal to an inner surface of the cathode shell or by providing a spark gap in the cavity of the conducting cathode shell. The electrons exit the cathode shell via the escape nozzle and are accelerated to the anode upon the application of a voltage pulse to the cathode. Still further, in a linear reverse cathode emission type of transducer, an anode is located at a first end of a transducer body and an emission element is located at a second end of the transducer body opposite the anode. The emission element is either a photoemission electron source or a thermionic emission surface, and generates electrons when activated by a light source. Furthermore, in a distally illuminated plasma cathode an anode is located at the first end of a transducer body and a cathode is located at a second end of a transducer body opposite to the anode. An ion and electron plasma is generated by applying a light pulse to the surface of the cathode. Electrons are extracted from the plasma by the application of a high voltage pulse to the anode. They are accelerated by the said high voltage pulse and strike the anode, where x-rays are produced.
Co-pending and commonly assigned U.S. patent application Ser. No. 09/504,709, filed Feb. 16, 2000, the contents of which are incorporated herein by reference, describes an explosive electron emission plasma cathode structure wherein one of the preferred embodiments utilizes liquid metal such as gallium-indium. The liquid metal is deposited inside a hollow, needle shaped, conducting cathode, which is made, for example, out of tungsten. A pre-pulse of voltage, typically 1-10 kV in magnitude, is applied to the cathode for duration of less than 100 microseconds. As a result, the surface of the liquid metal obtains the shape of a sharp tip having a typical diameter of 1-20 microns. A second pulse is then applied, typically of 10-100 kV, for duration of 1-100 nanoseconds. As a result, plasma is formed at the liquid metal tip. The high voltage pulse extracts electrons out of the plasma and accelerates them towards the anode. At the anode, the electrons"" kinetic energy is converted to x-ray photons and heat. Further still, in another preferred embodiment of said plasma cathode, the cathode may be an explosive electron emission cathode that contains a single carbon fiber or a bundle of carbon fibers. A high voltage pulse, of typical magnitude of 10-100 kV and typical duration of 1-100 nanoseconds, is applied to the cathode. As a result, part of the carbon fiber, or fibers"" tips is sublimated and plasma is formed. The high voltage pulse extracts electrons out of the plasma. These electrons are accelerated by the high voltage pulse towards the anode. At the anode, the electrons"" kinetic energy is converted to x-ray photons and heat.
Regardless of the type of anode and cathode structure utilized, an appropriate level of vacuum must be maintained within the transducer body. A vacuum is required to permit the production of electrons at the cathode, to enable uninterrupted acceleration of electrons from the cathode to the anode over a voltage difference that can typically vary from 10 kV to 100 kV, and to prevent high voltage breakdown within the transducer body, as breakdown probability is enhanced by ionization of the molecules of any residual gases present within the transducer body. The required vacuum level depends mainly on the electron production mechanism that is employed in the device. This level can vary from 10xe2x88x9210 Torr for x-ray emitters utilizing surface based electron emission mechanisms such as photo-emission or field emission, down to 10xe2x88x922 Torr or less for x-ray emitters employing pulsed plasma based mechanisms.
One of the major challenges in designing miniature x-ray transducers for in-situ use is maintaining the required vacuum level inside the transducer. The vacuum may be degraded due to several processes. Out-gassing from the electrodes and the insulating tube into the evacuated space is a major potential source of vacuum degradation. Other reasons for vacuum degradation include leaking of gases from outside the insulating tube through the walls of the insulating tube and seals and desorption of gases from the electrodes throughout the operation of the transducer.
The evacuated volume is about 10 mm3 as the transducer body is preferably several millimeters in length and about 1-2 mm in diameter. If a typical leak rate of gas into the cavity is 10xe2x88x9211 Torr-liter/sec, the pressure inside the cavity will rise at a rate of approximately 0.1 Torr/day. Unless a mechanism exists to absorb the entrant gases, the vacuum level will be quickly degraded to a point where x-ray emission is not possible. The above-mentioned analysis also applies to desorption of gases during the operation of the energy transducer. The surface area defining a cavity within the transducer body is about 30 mm2. Thus, the ratio of surface area to volume is approximately 3 mmxe2x88x921. The length and diameter of conventional x-ray tubes sized for most medical applications are about 100 times larger than the miniaturized energy transducer being considered, and conversely, the surface to volume ratio is 100 times smaller than that of the miniaturized energy transducer. As out-gassing is a major potential source-of vacuum degradation, the above mentioned comparison implies that for any given surface specific out-gassing rate the vacuum will be degraded 100 times faster in a miniaturized energy transducer than in a conventional x-ray tube. Thus, enhancing vacuum preservation before and throughout the operation of an x-ray emitting miniaturized energy transducer is particularly crucial.
In order to maintain the required vacuum level, getter material may be introduced through one or more components to the miniature x-ray transducer prior to final assembly thereof. Getter material is preferably made of titanium, zirconium, tantalum, iron, vanadium, aluminum or an alloy composed of two or more of these materials. Suitable types of getters for this application are, for example, non-evaporable sintered porous type getters such as ST701, ST702 and ST707 getter alloys, manufactured by SAES-getters, Milan, Italy. The getter material is activated by heating the miniature x-ray transducer to a temperature that is preferably 300xc2x0 C. or more. This heating step may be a by-product of the routine bake-out processes necessary to out-gas the x-ray emitting transducer before it is sealed off or can be performed as a separate manufacturing step. During the above mentioned heat activation process, the native oxide on the getter material surface is decomposed and oxygen diff-uses into the bulk of the getter material, exposing a fresh, ultra-clean surface of getter material. The resultant surface of the getter material has beneficial absorption characteristics, and can typically absorb gases, for example H2, CO, and H2O vapor. However, the getter material cannot absorb non-reactive gases such as all the noble gases and highly stable compounds such as Methane. Thus, the vacuum degradation problem is not eliminated completely by the use of getter material. This is represented by the following numerical example.
The following conditions are assumed: The electron production mechanism, which is employed within the miniature x-ray transducer, is such that the allowable operating pressure in the transducer is 10xe2x88x924 Torr. The required evacuated volume is 10 mm3 =10xe2x88x925 Liter. The lowest detectable leak rate of air with state of the art technology is 10xe2x88x9213 Torr-Liter/sec. The fraction of non-absorbable gases in air is 1%. The example intends to show the pressure rise within a miniature x-ray transducer with an expected shelf life of 100 days xcx9c107 sec. It is assumed that the pressure rise is due to leaking of non-absorbable gases alone.
Therefore, this pressure rise is:
(10xe2x88x9213 Torr-Liter/sec*1%*100 days)/10xe2x88x925 Liter =10xe2x88x923 Torr 
This result, 10xe2x88x923 Torr, is an order of magnitude above the maximum allowable pressure inside the transducer.
In addition, the space within the x-ray emitting transducer that is occupied by the getter material should be taken in consideration. This space is particularly limited inside miniature x-ray transducers intended for use inside the human body.
In view of the above, it is an object of the present invention to provide a mechanism for preserving the vacuum level in miniaturized energy transducers that emit x-rays, which removes stray gases regardless of their chemical reactivity, thus overcoming the problem of vacuum degradation due to non-absorbable gases.
It is another object of the present invention to provide a simple, inexpensive method to maintain vacuum level within a miniature x-ray emitter that does not require neither the introduction of getter material nor vacuum sealing prior to the assembly of the x-ray emitter.
Another object of the present invention to provide a device for in-situ x-ray radiation treatment that is easy to handle due to lack of vacuum sealed components and with relatively long shelf life due to the lack of need to maintain an appropriate vacuum level during the operation of the device alone.
The present invention provides a device and method for in-situ x-ray radiation treatment in humans, wherein different types of miniature energy transducers are utilized to emit x-rays. More specifically, an x-ray emitting energy transducer is provided that includes a transducer body having a first end and a second end, a cathode provided at the first end of the transducer body; and an anode provided at the second end of the transducer body. The transducer body, cathode, and anode define a cavity that communicates with an evacuation opening. A desired vacuum level is maintained within the cavity by evacuating the cavity through the evacuation opening with a dynamic pumping mechanism. The evacuation opening preferably extends through at least one of the anode, the cathode, and the transducer body.
An elongated flexible insertion device is also provided that includes an electrically conductive inner core, a dielectric material that surrounds the inner core, an outer shield that surrounds the dielectric material, an outer layer of electrical insulation that surrounds the outer shield; and a pumping conduit. In a preferred embodiment, the inner core is a hollow conduit that defines the pumping conduit. In another embodiment, the pumping conduit is embedded within the dielectric material. In a still further embodiment, the pumping conduit is coupled to the exterior of the outer layer of electrical insulation. Alternatively, the pumping conduit is embedded within the outer layer of electrical insulation.
The x-ray emitting energy transducer and flexible insertion device are coupled to an external unit that includes a power supply, a vacuum pump, a control unit and may optionally include a light source. In operation, the miniature x-ray energy transducer is positioned at a treatment site, evacuation of the miniature x-ray transducer is achieved to a desired vacuum level; and the miniature x-ray energy transducer is energized to achieve a predetermined radiation dosage. Stray gas molecules, that are either created during the operation of the miniature x-ray energy transducer or which diffuse into the transducer due to out gassing or leaks, are continuously evacuated during the operation of the miniature xray energy transducer in order to maintain the desired vacuum level. A dosimetry may optionally be provided to monitor the radiation dosage.
Other advantages and features of the invention will become apparent from the following detailed description of the preferred embodiments and the accompanying drawings.